The overall purpose of the grant is to further develop new techniques for studying fluid and solute exchange in lungs of both animal models and man. Three separate projects are included in this plan: (a) The rate at which radioactive extracellular indicators are lost from the lungs following administration in aerosols will be used to detect increases in the permeability of the epithelium covering the exchange areas of the lung. New indicators of different molecular weight will be used to determine if there is any loss in the ability of the epithelial cells to discriminate between small and large solutes (permselectivity) when the lungs are injured. Studies in animals will be focused on defining the size of these indicators and determining whether they become bound to substances such as surfactant within the lungs or trapped within the tissues. The suitability of the new indicators for detecting loss of permselectivity will be assessed in an animal model of lung injury and in patients with smoking history or lung diseases which alter epithelial permeability. A new approach for correcting the accumulation of radionuclides in the blood and tissues beyond the epithelium will be assessed in patients. These developments should further increase the usefulness of radioaerosol studies for detecting injuries of the epithelium in clinical and experimental contexts. The second part of the study is based on a new X-ray procedure for detecting cuffs of fluid around the arteries and veins in perfused lungs and watching the rates at which solutes exchange across the endothelium of vessels of different sizes. The role of diffusion and convection in the movement of radiopaque molecules will be studied and the local movement of nonradioactive dye out of individual vessels will be compared with the efflux of radioactive dye from the lungs. We anticipate that these experiments will shed new light on the manner in which fluid accumulates within the tissues of the lung when the lungs are injured or exposed to high intravascular pressures. In the third group of experiments, new methods of assessing the dilution of the fluid which covers the airspaces of the lung (ELF) when the lungs are lavaged (BAL) will be evaluated. These techniques are based upon (1) the concentrations of electrolytes in the BAL when the lungs are lavaged with nonelectrolyte solutions and (2) pre-equilibration of the organism with labeled chelates, the concentrations of which are kept at constant levels. If reliable methods can be derived for estimating how much ELF is diluted by BAL, it should be possible to determine the true, absolute concentrations of cells, proteins and small solutes normally present in ELF and how these are influenced by disease.